Background: Our aim was to determine the differences in short-term heart rate variability (HRV) between patients with metabolic syndrome (MS) and healthy controls. Methods: We searched electronic databases for primary works with short-term HRV recordings (≤30 min) that made comparisons between individuals with MS versus healthy controls. This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). Results: Twenty-eight articles were included in the qualitative synthesis and nineteen met the criteria for the MA. Patients with MS showed decreased SDNN (−0.36 [−0.44, −0.28], p < 0.001), rMSSD (−7.59 [−9.98, −5.19], p < 0.001), HF (−0.36 [−0.51, −0.20], p < 0.00001) and LF (−0.24 [−0.38, −0.1], p = 0.001). In subsequent subanalyses, we found a decrease in SDNN (−0.99 (−1.45, −0.52], p < 0.001), rMSSD (−10.18 [−16.85, −3.52], p < 0.01) and HF (−1.04 [−1.97, −0.1] p < 0.05) in women. In men, only LF showed a significant lower value (−0.26 [−0.5, −0.02], p < 0.05). We could not perform MA for non-linear variables. Conclusions: Patients with MS showed changes in time-domain analyses, with lower values in SDNN and rMSSD. Regarding frequency-domain analyses, MS patients showed a decrease in HF and LF When sex was used as a grouping variable, the MA was only possible in one of both sexes (men or women) in rMSSD and LF/HF. Lastly, when data for both men and women were available, subanalyses showed a different behavior compared to mixed analyses for SDNN, HF and LF, which might point towards a different impact of MS in men and women.

Heart failure (HF) is a common disease in which the heart cannot meet the metabolic demands of the body. It mostly occurs in individuals 65 years or older. Cardiac transplantation is the best option for patients with advanced HF. High numbers of patient-specific cardiac myocytes (CMs) can be generated from induced pluripotent stem cells (iPSCs) and can possibly be used to treat HF. While some studies found iPSC-CMS can couple efficiently to the damaged heart and restore cardiac contractility, almost all found iPSC-CM transplantation is arrhythmogenic, thus hampering the use of iPSC-CMs for cardiac regeneration. Studies show that iPSC-CM cultures are highly heterogeneous containing atrial-, ventricular- and nodal-like CMs. Furthermore, they have an immature phenotype, resembling more fetal than adult CMs. There is an urgent need to overcome these issues. To this end, a novel and interesting avenue to increase CM maturation consists of modulating their metabolism. Combined with careful engineering and animal models of HF, iPSC-CMs can be assessed for their potential for cardiac regeneration and a cure for HF.

Background: Our aim was to determine the impact that metabolic syndrome (MS) produces in long-term heart rate variability (HRV), quantitatively synthesizing the results of published studies to characterize the cardiac autonomic dysfunction in MS. Methods: We searched electronic databases for original research works with long-term HRV recordings (24 h) that compared people with MS (MS+) versus healthy people as a control group (MS−). This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). Results: A total of 13 articles were included in the qualitative synthesis, and 7 of them met the required criteria to be included in the MA. SDNN (−0.33 [−0.57, 0.09], p = 0.008), LF (−0.32 [−0.41, −0.23], p < 0.00001), VLF (−0.21 [−0.31, −0.10], p = 0.0001) and TP (−0.20 [−0.33, −0.07], p = 0.002) decreased in patients with MS. The rMSSD (p = 0.41), HF (p = 0.06) and LF/HF ratio (p = 0.64) were not modified. Conclusions: In long-term recordings (24 h), SDNN, LF, VLF and TP were consistently decreased in patients with MS. Other parameters that could be included in the quantitative analysis were not modified in MS+ patients (rMSSD, HF, ratio LF/HF). Regarding non-linear analyses, the results are not conclusive due to the low number of datasets found, which prevented us from conducting an MA.

Background/Objectives: Heart rate variability (HRV) is a reliable, non-invasive marker of autonomic nervous system function and is often impaired in individuals with metabolic syndrome (MetS). Physical exercise has emerged as an effective strategy to improve autonomic modulation; however, the comparative effects of different training modalities on HRV in individuals with MetS remain unclear. This systematic review and meta-analysis aimed to evaluate the impact of various exercise interventions on HRV and to identify which training types yield the most significant improvements. Methods: A systematic search was conducted in PubMed and Scopus up to April 2025. Eligible studies (n = 16) included adults with obesity and MetS (n = 752) who underwent structured exercise interventions with HRV assessments pre- and post-intervention. Standardized mean differences were calculated using random effects models. Subgroup analyses were performed based on training modality (endurance training [ET], resistance training [RT], high-intensity interval training [HIIT], and concurrent training [CT]). Results: Sixteen studies of moderate to high quality were included, with eleven studies eligible for meta-analysis. ET and HIIT significantly improved time-domain indices (Root mean square of differences of successive R-R intervals —rMSSD—, Standard deviation of the R-R interval series —SDNN—) and frequency-domain parameters (high-frequency —HF—), suggesting enhanced parasympathetic activity. RT showed inconsistent effects, while CT improved long-term HF and total power (TP). Non-linear indices were the least reported due to insufficient data. Conclusions: Physical exercise—particularly ET and HIIT—appears to enhance cardiac autonomic modulation in individuals with obesity and MetS. These findings support incorporating targeted training strategies into clinical practice to optimize cardiovascular health in these populations.

Metabolic syndrome (MetS) drives cardiac remodeling and fibrosis, contributing to diastolic dysfunction and heart failure with preserved ejection fraction, but chamber-specific mechanisms remain poorly defined. New Zealand White rabbits were fed a high-fat/high-sucrose diet for 28 weeks to induce experimental MetS. Systemic phenotype, cardiac structure (echocardiography), myocardial fibrosis (Picrosirius red histology), myosin/collagen gene expression (qRT-PCR), and chamber-specific proteomics were assessed across left/right atria and ventricles. The model reproduced central obesity, glucose intolerance, dyslipidemia, and mild hypertension, with concentric left ventricular hypertrophy and selective ventricular fibrosis, as follows: increased collagen in left ventricle (LV) and right ventricle (RV), unchanged in atria. Ventricular α-myosin heavy-chain gene expression was upregulated, while collagen I and α-smooth muscle actin transcripts showed ventricular-specific downregulation. Proteomics revealed atrial metabolic and cytoskeletal adaptations with minimal extracellular matrix involvement; ventricles displayed early profibrotic cues (galectin-3 in LV), metabolic inefficiency (impaired glycolysis/ATP production in LV; lipid oxidation shift in RV), and diminished provisional matrix support. Conclusions: concentric LV hypertrophy and great vessel enlargement occurred without systolic/diastolic dysfunction; ventricular-selective fibrosis, α-myosin heavy-chain upregulation, type I collagen/α-smooth muscle actin downregulation, and chamber-specific proteomic changes showed atrial adaptation versus ventricular early profibrotic/metabolic inefficiency.

Rnd3 is an atypical member of the Rho GTPase family whose activity is mainly regulated by expression, localization and protein stability rather than canonical GDP/GTP cycling. In cancer, Rnd3 has been described both as a tumor suppressor and as a tumor-promoting factor, creating an apparent functional paradox. We propose that this paradox is resolved by a mechanistic invariant: Rnd3 exerts a conserved inhibition of RhoA/ROCK1-dependent actomyosin contractility, whose phenotypic output is redirected by context-specific accessory effectors rather than reversed. In this review, we revisit this paradox by integrating evidence from mechanistic studies, tumor models and patient-associated datasets. We propose that Rnd3 should not be interpreted through a binary oncogene/tumor-suppressor framework, but rather as a context-dependent regulator of tumor cell state. In many tumor settings, Rnd3 repression or loss of Rnd3 function favors proliferation, apoptosis resistance and therapy resistance through pathways involving Notch, NF-κB, EGFR/ERK, EZH2-dependent chromatin regulation, m6A-mediated RNA control, microRNAs and chaperone-mediated autophagy. However, in selected contexts, including RTK-driven glioblastoma, hepatocellular carcinoma, non-small-cell lung cancer, melanoma and gastric cancer, Rnd3 may support tumor fitness, migration or invasive plasticity. We therefore propose a functional stratification model in which Rnd3 output depends on the biological process, tumor lineage, pathway activity and mechanical state of the cell.